1. Field of the Invention
The present invention relates to a novel montelukast amine salt, and a method for preparing a montelukast sodium salt by using the same.
2. Description of the Prior Art
A montelukast sodium salt, as represented by Formula 1 below, is a leukotriene receptor antagonist. Leukotriene is related to contraction and inflammation of airway muscles, and fluid. accumulation within the lung, and is currently useful as a therapeutic agent for respiratory system diseases such as asthma and allergic rhinitis. Montelukast sodium salt was first developed by Merck & Co., Inc. and is commercially available as Singulair®, which is a moisture-absorbing and optically active white (or pale white) powder having the structural formula below, and is soluble in methanol, ethanol or water, and insoluble in acetonitrile.

Since a montelukast sodium salt contains an asymmetric carbon atom, it is very difficult to secure chiral purity of montelukast and obtain a highly pure montelukast sodium salt.
In synthesis of a montelukast sodium salt, a low yield and a difficult purification process have been always problematic due to the complicated purification method.
First, Korean Registered Patent No. 227716, and EU Patent No. 480717 disclosed a method for synthesizing montelukast acid, represented by Reaction Scheme 1 below. However, the preparation method requires not only an additional process for introducing and removing a tetrahydropyranyl protecting group, but also a purification process through chromatography. Thus, it is difficult to employ the method in mass production. Furthermore, there is a problem in that the method is not suitable for mass production due to a low yield.

Korean Registered Patent No. 899585 disclosed a montelukast isopropylamine salt prepared by Reaction Scheme 2 below, and a method for preparing a montelukast sodium salt by using the same salt. However, there are disadvantages such as a low yield of isopropylamine salt and a low total yield of sodium salt.

International Publication WO 2007/004237 disclosed a method for preparing a montelukast sodium salt by using α-methyl benzylamine. However, in the method, the purity and yield are not described. Also, Korean Registered Patent No. 920314 disclosed a method for preparing a montelukast sodium salt by using a montelukast benzylamine salt. However, the method has a problem in that the total yield of the benzylamine salt is significantly low (about 50%), and also the yield of the sodium salt is low.
Accordingly, in order to solve problems (such as low purity, and low yield) in a method for preparing a montelukast sodium salt by using conventionally known salts of montelukast, the inventors of the present invention have struggled to research a novel salt of montelukast. As a result, they have completed the present invention by developing a novel montelukast 4-halobenzylamine salt. Through the developed novel montelukast amine salt, it is possible to prepare a montelukast sodium salt with a high purity and a high yield, compared to conventionally disclosed methods. Thus, it is possible to very economically and efficiently mass-produce the montelukast sodium salt.